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Introduction: The presence of cerebral-cardiac syndrome, wherein brain diseases coincide with heart dysfunction, significantly impacts patient prognosis. In severe instances, circulatory failure may ensue, posing a life-threatening scenario necessitating immediate life support measures, particularly effective circulatory support methods. The application of extracorporeal membrane oxygenation (ECMO) is extensively employed as a valuable modality for delivering circulatory and respiratory support in the care of individuals experiencing life-threatening circulatory and respiratory failure. This approach facilitates a critical temporal window for subsequent interventions. Consequently, ECMO has emerged as a potentially effective life support modality for patients experiencing severe circulatory failure in the context of cerebral-cardiac syndrome. However, the existing literature on this field of study remains limited. Case description: In this paper, we present a case study of a patient experiencing a critical cerebral-cardiac syndrome. The individual successfully underwent veno-arterial-ECMO (VA-ECMO) therapy, and the patient not only survived, but also received rehabilitation treatment, demonstrating its efficacy as a life support intervention. Conclusion: VA-ECMO could potentially serve as an efficacious life support modality for individuals experiencing severe circulatory failure attributable to cerebral-cardiac syndrome.

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Background: Pulmonary embolism is a condition of right cardiac dysfunction due to pulmonary circulation obstruction. Malignant tumor-induced pulmonary embolism, which has a poor therapeutic outcome and a significant impact on hemodynamics, is the cause of sudden death in patients with malignant tumors. Case description: A 38-year-old female patient, who had a medical history of right renal hamartoma, and right renal space-occupying lesion, was admitted to the hospital. During the procedure to resect the right renal malignancy, the blood pressure and end-tidal carbon dioxide level dropped, and a potential pulmonary embolism was considered as a possibility. After inferior vena cava embolectomy, the hemodynamics in the patient remained unstable. The successful establishment of venoarterial extracorporeal membrane oxygenation (VA-ECMO) resulted in the stabilization of her hemodynamics and ventilation. On Day 2 of VA-ECMO support, her respiration and hemodynamics were relatively stable, and ECMO assistance was successfully terminated following the "pump-controlled retrograde trial off (PCRTO)" test on Day 6. The patient improved gradually after the procedure and was discharged from the hospital after 22 days. Conclusion: VA-ECMO can be used as a transitional resuscitation technique for patients with massive pulmonary embolism. It is critical for the perfusion of vital organs and can assist with surgical or interventional treatment, lower right heart pressure, and hemodynamic stability. VA-ECMO has a significant impact on patient prognosis and can reduce the mortality rate.

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Vascular endothelial cells (VECs) are located between the blood plasma and the vascular tissue, and the ferroptosis (iron-dependent programmed cell death) of VECs can lead to a range of cardiovascular diseases. Icariin is the main active ingredient of Epimedium brevicornum Maxim., which can improve endothelial cell dysfunction. In the present study, the protective effects of icariin on oxidised low-density lipoprotein (ox-LDL)-treated VECs and high-fat diet-fed Apolipoprotein E-deficient mice were investigated. Inflammatory fibrosis in tissues and inflammatory factors in serum and cell supernatants were detected, and mitochondrial membrane potential and the expression levels of ferroptosis-associated proteins were also detected. The results revealed that icariin reduced the endothelial atherosclerotic plaque area and collagen fibres in aortic sinus tissue, and increased the viability and mitochondrial membrane potential, whereas it reduced the reactive oxygen species levels of VECs. The nucleation of transcription factor EB (TFEB) and subsequent autophagy were negatively associated with ferroptosis in endothelial cells, and the more prominent the autophagy, the lower the levels of ferroptosis. Furthermore, by co-treating the cells with icariin and the two autophagy inhibitors, Bafilomycin A1 (blocking autophagosome and lysosome fusion) and 3-methyladenine (blocking autophagosome formation), respectively, the promoting effects of icariin on autophagy were found to be mediated through the process of autophagosome-lysosome fusion. In in vivo experiments, icariin reduced ferroptosis, alleviated atherosclerotic lesions and increased the rate of TFEB nucleation. Additionally, it was found that ARG304, THR308 and GLN311 were the optimal binding sites for the interaction between icariin and TFEB. Taken together, these results suggest that the fusion of autophagosomes and lysosomes promoted by icarrin enhances autophagy and thus reduces ferroptosis. Therefore, icariin may be a potential candidate for the prevention of ferroptosis of VECs and, thus, for the treatment of cardiovascular diseases.

Asunto(s)

Aterosclerosis , Enfermedades Cardiovasculares , Ferroptosis , Ratones , Animales , Células Endoteliales/metabolismo , Aterosclerosis/metabolismo , Autofagia

RESUMEN

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) has spread widely around the world with strong infectivity, rapid mutation and a high mortality rate. Mechanical ventilation has been included in the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 8) as an important treatment for severe and critical COVID-19 patients, but its clinical efficacy in COVID-19 patients is various. Therefore, it is necessary to study the influencing factors on the efficacy of mechanical ventilation in severe and critical COVID-19 patients. AIM: The aim of this study was to determine the influencing factors on the efficacy of mechanical ventilation in severe and critical COVID-19 patients. METHODS: A total of 27 severe and critical COVID-19 patients were enrolled in this study and treated with mechanical ventilation at the Optical Valley Campus of Hubei Maternal and Child Health Care Hospital (Wuhan, Hubei Province) from February 20, 2020 to April 5, 2020. According to the final treatment outcomes, the patients were divided into the "effective group" and "death group." The clinical data of the two groups, such as the treatment process and final outcome, were retrospectively analyzed in order to determine the specific curative effects on the two groups and the reasons for the differences in such curative effects, as well as to explore the factors related to death. RESULTS: This study enrolled 27 severe and critical COVID-19 patients, including 17 males (63.0%) and 10 females (37.0%). Their ages were 74.41 ± 11.73-years-old, and 19 patients (70.4%) were over 70-years-old. Severe COVID-19 patients over 70-years-old who were treated with mechanical ventilation died in 14 cases (82.4%); thus, this was the peak age. A total of 17 patients died of basic disease, 16 of whom had more than two basic diseases. The basic diseases were hypertension, diabetes, and cardiovascular and cerebrovascular diseases. At the same time, 13 patients (76.5%) died from an abnormal increase in blood glucose. Among them, eight had diabetes before contracting COVID-19 and five had a stress-induced increase in blood glucose after contracting COVID-19. Diabetic ketoacidosis occurred in one case. The use of tocilizumab may be a double-edged sword that carries a certain risk in clinical usage. Among the patients who died, 16 (94.1%) went into septic shock at the end. There were significant differences in the degree of infection, cardiac and renal function, and blood glucose between the death group and effective group. CONCLUSION: Age, blood glucose, cardiac and renal function, and inflammatory reaction are important indicators of poor prognosis for mechanical ventilation in severe and critical COVID-19 patients.

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Osteosarcoma, a common type of bone cancer in children, and represents an aggressive and fetal cancer worldwide. Osteosarcoma initiating cells are considered to be a subpopulation of cancer cells which contribute to the progression, recurrence, metastasis and multi-drug resistance of osteosarcoma. CD133 is considered to be one marker for osteosarcoma initiating cells. All-trans retinoic acid (ATRA), an active metabolite of vitamin A under the family retinoid, is an up-and-coming drug which was able to effectively treat various cancer initiating cells. Nevertheless, there have been no research that reported the activity of ATRA against osteosarcoma initiating cells. In this research, we hereby examined the potential activity of ATRA in osteosarcoma initiating cells, and developed lipid-polymer nanoparticles with CD133 aptamers for targeted ATRA delivery to osteosarcoma initiating cells. Using the cytotoxicity assay, colony formation assay, tumorsphere formation assay and flow cytometry, the therapeutic effect of ATRA and ATRA-loaded lipid-polymer nanoparticles conjugated with CD133 aptamers (ATRA-PLNP-CD133) against osteosarcoma initiating cells were investigated. The results showed that ATRA exerted potent activity towards osteosarcoma initiating cells. ATRA-PLNP-CD133, which showed a size of 129.9 nm and a sustained release of ATRA during 144 h, was demonstrated to efficiently and specifically promote the ATRA delivery to osteosarcoma initiating cells, and achieve superior therapeutic efficacy in osteosarcoma compared with ATRA and non-targeted nanoparticles. This is the first report of the therapeutic efficacy of ATRA towards osteosarcoma initiating cells, and the increased ATRA delivery by nanoparticles to osteosarcoma initiating cells using CD133 aptamers. ATRA-PLNP-CD133 represent an up-and coming approach for the therapy of osteosarcoma initiating cells.

Asunto(s)

Antígeno AC133/administración & dosificación , Aptámeros de Nucleótidos/administración & dosificación , Neoplasias Óseas/tratamiento farmacológico , Nanopartículas/administración & dosificación , Osteosarcoma/tratamiento farmacológico , Tretinoina/administración & dosificación , Antígeno AC133/genética , Animales , Antineoplásicos/administración & dosificación , Aptámeros de Nucleótidos/genética , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Relación Dosis-Respuesta a Droga , Sistemas de Liberación de Medicamentos/métodos , Humanos , Lípidos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Osteosarcoma/genética , Osteosarcoma/patología , Polímeros/administración & dosificación , Ensayos Antitumor por Modelo de Xenoinjerto/métodos

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Aim of the present work was to investigate the clinical efficacy of Kuntai capsule in the treatment of postmenopausal women with endometriosis, Breast pain and Vaginal Bleeding. 120 elderly female outpatients over 50 years old with Breast pain were randomly divided into control group (60 cases) and observation group (60 cases). All patients were given diclofenac sodium enteric-coated tablets 25mg, 3 times a day. The observation group was given additional Kuntai capsules at a dose of 4 capsules per time, 3 times a day. Serum estradiol (E2), follicle stimulating hormone (FSH), and luteinizing hormone (LH) were detected in all patients before and at 12 weeks after treatment. Modified Kupperman score (K score) for evaluating menopausal symptoms. The post therapeutic serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) level and endometrial thickness decreased significantly (p<0.05). After treatment, KMI scores of kunati group was significantly decreased compared with baseline (<0.01) and there was no significant difference between groups (p>0.05). After treatment, hot flush and insomnia scores were both improved significantly. After therapy, serum E2 level obviously higher than the control groups, while FSH and LH levels were obviously lower (p<0.05). The incidence of vaginal bleeding, breast distending pain in group was obviously higher in control group than Kuntai group. Thus, Kuntai capsule improved the ovarian function of patients, raised the level of estrogen in vivo and alleviates the clinical manifestations of Breast pain.

Asunto(s)

Medicamentos Herbarios Chinos/uso terapéutico , Mastodinia/tratamiento farmacológico , Posmenopausia , Hemorragia Uterina/tratamiento farmacológico , Estrógenos/sangre , Estrógenos/metabolismo , Femenino , Hormona Folículo Estimulante/sangre , Humanos , Persona de Mediana Edad

RESUMEN

We previously developed salinomycin (sali)-entrapped nanoparticles labeled with CD133 aptamers which could efficiently eliminate CD133+ osteosarcoma cancer stem cells (CSCs). However, sufficient evidences suggest that the simultaneous targeting both CSCs and cancer cells is pivotal in achieving preferable cancer therapeutic efficacy, due to the spontaneous conversion between cancer cells and CSCs. We hereby constructed sali-entrapped lipid-polymer nanoparticles labeled with CD133 and EGFR aptamers (CESP) to target both osteosarcoma cells and CSCs. The cytotoxicity of CESP in osteosarcoma cells and CSCs was superior to that of single targeting or nontargeted sali-loaded nanoparticles. Administration of CESP in vivo showed the best efficacy in inhibiting tumor growth than other controls in osteosarcoma-bearing mice. Thus, CESP was demonstrated to be capable of efficiently targeting both osteosarcoma CSCs and cancer cells, and it represents an effective potential approach to treat osteosarcoma.

Asunto(s)

Aptámeros de Nucleótidos/química , Neoplasias Óseas/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Nanopartículas/administración & dosificación , Células Madre Neoplásicas/efectos de los fármacos , Osteosarcoma/tratamiento farmacológico , Piranos/administración & dosificación , Antígeno AC133/química , Animales , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Proliferación Celular/efectos de los fármacos , Receptores ErbB/química , Femenino , Humanos , Lípidos/química , Ratones , Ratones Desnudos , Nanopartículas/química , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Osteosarcoma/metabolismo , Osteosarcoma/patología , Polímeros/química , Piranos/farmacología , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto

RESUMEN

Osteosarcoma is a common childhood bone cancer with a poor survival rate. Osteosarcoma cancer stem cells (CSCs) contribute to the recurrence, drug resistance and metastasis of this disease. Previous evidence suggested that cancer cells are able to spontaneously turn into CSCs, thus it is crucial to simultaneously target osteosarcoma cells and CSCs. Our previous studies have demonstrated that salinomycin preferably eliminated osteosarcoma CSCs. In addition, amplification of the epidermal growth factor receptor (EGFR) is a common genetic aberration in osteosarcoma, and thus EGFR is a promising target in osteosarcoma. The present study aimed to develop EGFR aptamer-conjugated salinomycin-loaded polymer-lipid hybrid nanoparticles (EGFR-SNPs) to target both osteosarcoma cells and CSCs. The results revealed that EGFR was overexpressed in these cells, and that EGFR-SNPs possessed a small size of 95 nm, suitable drug encapsulation efficiency (63%) and sustained drug release over 120 h. EGFR-SNPs targeted EGFR-overexpressing osteosarcoma cells and CSCs, resulting in an enhanced cytotoxic effect compared with non-targeted SNPs and salinomycin. Notably, EGFR-SNPs was able to reduce the osteosarcoma tumorsphere formation rate and proportion of CD133+ osteosarcoma CSCs in the osteosarcoma cell lines more effectively compared with SNPs and salinomycin, suggesting that EGFR-SNPs effectively reduced the proportion of osteosarcoma CSCs. In conclusion, the interaction of EGFR aptamers and EGFR is a potential approach to promote the effective delivery of salinomycin to osteosarcoma. The study results suggested that EGFR-SNPs represents a promising approach to target osteosarcoma cells and CSCs.

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Pituitary tumors may secrete hormones that affect pregnancy. Pregnancy also induces pituitary tumor growth; however, how pregnancy increases the growth of pituitary tumors remains unclear. The present study investigated pregnant female mice with subcutaneous pituitary tumors. The time of tumor occurrence and tumor weight were detected in pregnant and control mice. Tumor weights were measured at the end of the experiment. Blood was collected from pregnant and control mice. Brain-derived neurotrophic factor (BDNF) levels in the blood were detected using an ELISA kit. The in vitro effects of BDNF on pituitary tumor AtT-20 cell proliferation and cell cycle were investigated. It was revealed that pregnancy promoted the growth of pituitary tumors. In comparison to non-pregnant mice, the pregnant mice exhibited increased BDNF levels in the blood. In vitro BDNF treatment was able to increase the rate of proliferation of pituitary tumor cells. Additional cell cycle analysis revealed that BDNF was able to alter the cell cycle distribution of pituitary tumor cells. These results indicated that pregnancy was able to increase the BDNF level and promote the growth of pituitary tumor cells by increasing the rate of the cell cycle, leading to increased tumor growth rate in vivo. The present study provides insights into how pregnancy affects the growth of pituitary tumors. Therefore, it may be beneficial to perform pituitary tumor diagnosis or therapy on pregnant patients.

RESUMEN

To investigate the inhibitory effect of Huangqi Danshen decoction (HDD) on isoproterenol (ISO)-induced myocardial remodeling and explore its effect on STIM1, TRPC1, CaN and NFATc3 expressions. ISO (2.5 mg•kg⁻¹â€¢d⁻¹×14 d) was given by subcutaneous injection to establish myocardial remodeling models in rats, and then were randomly divided into control group, ISO model group, HDD5 group (HDD 5 g•kg⁻¹â€¢d⁻¹+ISO), and HDD10 group (HDD 10 g•kg⁻¹â€¢d⁻¹+ISO). After intervention for 4 weeks, the heart mass index (HW/BW) and the left ventricular mass index (LVW/BW) were calculated; the structure of myocardium was observed by echocardiography; the pathological changes of myocardium were observed by HE staining; levels of BNP, CaN and CaM kinases II in serum were detected by ELISA, and the protein expression levels of STIM1, TRPC1, p-CaN, p-NFATc3, and NFATc3 in left ventricular tissues were detected by Western blot. The results showed that the HW/BW and LVW/BW in ISO group were greater than those in HDD5 group and HDD10 group (P<0.05); Echocardiography showed that HDD inhibited ISO-induced increase in LVEDD and LVESD; ELISA results showed that HDD could significantly inhibit the increase of BNP, CaN and CaM kinases II levels in serum of rats with ISO-induced myocardial remodeling (P<0.01). Western blot results showed that STIM1, TRPC1, p-CaN, p-NFATc3 and NFATc3 expression levels were increased in the myocardial tissues of ISO group rats, and after HDD administration, the above expression levels were decreased in group ISO, HDD for myocardial tissue after administration of STIM1, TRPC1, p-CaN, p-NFATc3 and NFATc3 expression decreased (P<0.05). Our findings indicated that HDD can attenuate the myocardial remodeling induced by ISO, and its mechanism may be related to down-regulating the expression levels of STIM1, TRPC1, CaM kinases II, p-CaN/CaN and p-NFATc3/NFATc3.

Asunto(s)

Medicamentos Herbarios Chinos/farmacología , Corazón/efectos de los fármacos , Factores de Transcripción NFATC/metabolismo , Salvia miltiorrhiza/química , Molécula de Interacción Estromal 1/metabolismo , Canales Catiónicos TRPC/metabolismo , Remodelación Ventricular , Animales , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Isoproterenol , Miocardio , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Ratas Wistar

RESUMEN

BACKGROUND: We aimed to evaluate an approach to induced abortions during early pregnancies that controls the suction pressure and restricts the duration of the procedure. METHODS: Three hundred patients programmed for induced early pregnancy abortions, hospitalized in the Shandong Provincial Maternity & Child-care Hospital from October 2013 to October 2015, were enrolled. Patients were randomly assigned to either research or control group. In the research group, operation pressure was controlled at 400 mmHg and operation time in the uterine cavity was kept at less than 75 s. In the control group, pressure ranged from 400-500 mmHg. Clinical variables were recorded for each patient until the fourth month after surgery, correlation and multivariate analyses were carried. RESULTS: Compared with control group, anesthesia and intervention durations and the suction pressure were significantly lower and the endometrial thickness of the first late follicular phase after operation was significantly larger in the research group (P<0.05). In the first postoperative month, the number of patients who reported menstruation flow decreased by more than 1/3 of its normal volume was significantly lower than that in the control group (P<0.05). In the third postoperative month, the thickness of the late follicular phase endometrium was significantly larger than that in the control group (P<0.001). The mean intraoperative pressure and intrauterine operation duration both influenced the endometrial thickness of follicular phase. CONCLUSION: Controlling the suction pressure and time for vacuum aspiration abortions during early pregnancies can reduce the incidence of intrauterine adhesions and better protect the endometrium.

RESUMEN

Organotin compounds have been widely used in recent decades, however, the residential tributyltin (TBT) in environment has potential harmful effects on human health due to the disruption of endocrine system even at trace level. Herein, this work reports on an effective electro-field-assisted-photocatalytic technique for removal of TBT by applying an electric field to photocatalysis of as-prepared hierarchical TiO2 microspheres. The synthesis of catalytic materials is based on a self-assembly process induced by microwave-assisted solvothermal reaction. Hierarchical TiO2 microspheres consisting of nanowires can be obtained in short time with this facile method and possess high surface area and superior optical properties. As the catalyst, it was found that the reaction rate constant of electro-field-assisted-photocatalytic removal (0.0488 min-1) of TBT exhibited almost a 9 fold improvement as compared to that of photocatalysis (0.0052 min-1). The proposed mechanism of electro-field-assisted-photocatalytic removal of TBT was verified by using 117Sn-enriched TBT spike solution as an isotopic tracer. In addition, varying impacts from some key reaction conditions, such as voltage of potential, pH value and the presence of Cr and formaldehyde were also discussed. The overall satisfactory TBT removal performance of the proposed electro-field-assisted-photocatalysis procedure with hierarchical TiO2 microspheres, which was validated using actual tannery wastewater samples from three different kinds of tanning procedures. These attributes suggest that this electro-field-assisted-photocatalysis may have broad applications for the treatment of tannery wastewater.

Asunto(s)

Microesferas , Titanio/química , Compuestos de Trialquiltina/aislamiento & purificación , Aguas Residuales/química , Purificación del Agua/métodos , Catálisis , Técnicas Electroquímicas/métodos , Microondas , Curtiembre

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BACKGROUND: This study aimed to assess the efficacy and safety of drotaverine hydrochloride (DHC) in Chinese patients with irritable bowel syndrome (IBS). METHODS: Totally, 144 patients with IBS were included and randomly divided into treatment group and placebo group in a 1:1 ratio. Patients received either DHC or placebo 80-mg tablet, 3 times daily for a total of 4 weeks. The primary outcome included abdominal pain, measured by the visual analog scale (VAS), and weekly stool frequency. The secondary outcomes were measured by the Bristol scale, and the 36-item short form health survey (SF-36), as well as the adverse events recorded during the treatment period. All those outcomes were measured at the end of 4-week treatment. RESULTS: The total and different types of IBS in VAS, stool frequency, and Bristol score were significantly better in the treatment group than those in the placebo group at the end of 4-week treatment. However, no significant difference was found in quality of life, measured by SF-36 scale between 2 groups. Additionally, no serious and significant differences in adverse events were found in and between both groups. CONCLUSION: The findings suggest that DHC has promising efficacy to enhance symptoms of IBS in Chinese population.

Asunto(s)

Síndrome del Colon Irritable/diagnóstico , Síndrome del Colon Irritable/tratamiento farmacológico , Papaverina/análogos & derivados , Seguridad del Paciente , Administración Oral , Adulto , Anciano , Distribución de Chi-Cuadrado , China , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Papaverina/uso terapéutico , Medición de Riesgo , Índice de Severidad de la Enfermedad , Método Simple Ciego , Estadísticas no Paramétricas , Resultado del Tratamiento , Adulto Joven

RESUMEN

Axonal degeneration is a common pathological change of neurogenical disease which often arises before the neuron death. But it had not found any effective method to protect axon from degeneration. In this study we intended to confirm the protective effect of nicotinamide adenine dinucleotide (NAD), investigate the optimal administration dosage and time of NAD, and identify the relationship between silence signal regulating factor 1 (SIRT1) and axonal degeneration. An axonal degeneration model was established using dorsal root ganglion (DRG) neurons injured by vincristine to observe the protective effects of NAD to the injured axons. In addition, the potential contribution of the SIRT1 in axonal degeneration was also investigated. Through the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, immunochemistry staining, axons counting and length measuring, transmission electron microscope (TEM) observation, we demonstrated that NAD played an important role in preventing axonal degeneration. Further study revealed that the expression of SIRT1 and phosphorylated Akt1 (p-Akt1) was up-regulated when NAD was added into the culturing medium. Taking together, our results demonstrated that NAD might delay the axonal degeneration through SIRT1/Akt1 pathways.

Asunto(s)

Axones/patología , NAD/metabolismo , Degeneración Nerviosa/metabolismo , Fármacos Neuroprotectores/farmacología , Sirtuina 1/efectos de los fármacos , Animales , Antineoplásicos Fitogénicos/toxicidad , Axones/efectos de los fármacos , Recuento de Células , Ganglios Espinales/citología , Ganglios Espinales/efectos de los fármacos , Neuritas/efectos de los fármacos , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Vincristina/toxicidad

RESUMEN

Four dinuclear trivalent lanthanide complexes of the general formula [Ln2(2-Br-5-MOBA)6(phen)2] (Ln = Nd(), Sm(), Ho(), Er(); 2-Br-5-MOBA = 2-bromine-5-methoxybenzoate, phen = 1,10-phenanthroline) were prepared and structurally characterized. The complexes to are isostructural with a coordination number of nine. The carboxylic acid ligands adopt bridging, bidentate chelating, and tridentate chelating bridging modes to coordinate with Ln(iii) ions. The structures of the complexes were confirmed on the basis of elemental analysis, molar conductance, thermogravimetric analysis (TGA), and IR and UV spectra. The heat capacities and thermal circulating processes of the prepared complexes were performed on a differential scanning calorimeter under a nitrogen atmosphere. Two remarkable solid-solid phase transitions existed both in the heat capacities and thermal circulating processes. The bacteriostatic activities of the complexes were evaluated against Candida albicans, Escherichia coli and Staphylococcus aureus. Besides, the luminescent property of complex was also investigated, and the magnetic properties of complexes and were also discussed in detail.

RESUMEN

Members of the calmodulin-binding transcription activator (CAMTA) family of proteins function as calcium-sensitive regulators of gene expression in multicellular organisms ranging from plants to humans. Here, we show that global or nervous system deletion of CAMTA1 in mice causes severe ataxia with Purkinje cell degeneration and cerebellar atrophy, partially resembling the consequences of haploinsufficiency of the human CAMTA1 locus. Gene-expression analysis identified a large collection of neuronal genes that were dysregulated in the brains of CAMTA1-mutant mice, and elucidation of a consensus sequence for binding of CAMTA proteins to DNA revealed the association of CAMTA-binding sites with many of these genes. We conclude that CAMTA1 plays an essential role in the control of Purkinje cell function and survival. CAMTA1-mutant mice provide a model to study the molecular mechanisms of neurodegenerative diseases and for screening potential therapeutic interventions for such disorders.

Asunto(s)

Ataxia/metabolismo , Ataxia/patología , Proteínas de Unión al Calcio/deficiencia , Células de Purkinje/metabolismo , Células de Purkinje/patología , Transactivadores/deficiencia , Factores de Transcripción/deficiencia , Secuencia Rica en At , Animales , Ataxia/fisiopatología , Secuencia de Bases , Sitios de Unión , Proteínas de Unión al Calcio/metabolismo , Regulación de la Expresión Génica , Integrasas/metabolismo , Secuencias Invertidas Repetidas/genética , Masculino , Ratones , Ratones Noqueados , Datos de Secuencia Molecular , Actividad Motora , Nestina/metabolismo , Motivos de Nucleótidos/genética , Multimerización de Proteína , Transactivadores/metabolismo , Factores de Transcripción/metabolismo

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The adult mammalian heart has limited potential for regeneration. Thus, after injury, cardiomyocytes are permanently lost, and contractility is diminished. In contrast, the neonatal heart can regenerate owing to sustained cardiomyocyte proliferation. Identification of critical regulators of cardiomyocyte proliferation and quiescence represents an important step toward potential regenerative therapies. Yes-associated protein (Yap), a transcriptional cofactor in the Hippo signaling pathway, promotes proliferation of embryonic cardiomyocytes by activating the insulin-like growth factor and Wnt signaling pathways. Here we report that mice bearing mutant alleles of Yap and its paralog WW domain containing transcription regulator 1 (Taz) exhibit gene dosage-dependent cardiac phenotypes, suggesting redundant roles of these Hippo pathway effectors in establishing proper myocyte number and maintaining cardiac function. Cardiac-specific deletion of Yap impedes neonatal heart regeneration, resulting in a default fibrotic response. Conversely, forced expression of a constitutively active form of Yap in the adult heart stimulates cardiac regeneration and improves contractility after myocardial infarction. The regenerative activity of Yap is correlated with its activation of embryonic and proliferative gene programs in cardiomyocytes. These findings identify Yap as an important regulator of cardiac regeneration and provide an experimental entry point to enhance this process.

Asunto(s)

Proteínas Adaptadoras Transductoras de Señales/metabolismo , Corazón/fisiología , Miocitos Cardíacos/fisiología , Fosfoproteínas/metabolismo , Regeneración/fisiología , Transducción de Señal/fisiología , Factores de Transcripción/metabolismo , Aciltransferasas , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Western Blotting , Proteínas de Ciclo Celular , Cartilla de ADN/genética , Ecocardiografía , Vía de Señalización Hippo , Técnicas Histológicas , Ratones , Ratones Transgénicos , Mutación Missense/genética , Contracción Miocárdica/genética , Contracción Miocárdica/fisiología , Miocitos Cardíacos/metabolismo , Fosfoproteínas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Sales de Tetrazolio , Factores de Transcripción/genética , Proteínas Señalizadoras YAP

RESUMEN

The epicardium encapsulates the heart and functions as a source of multipotent progenitor cells and paracrine factors essential for cardiac development and repair. Injury of the adult heart results in reactivation of a developmental gene program in the epicardium, but the transcriptional basis of epicardial gene expression has not been delineated. We established a mouse embryonic heart organ culture and gene expression system that facilitated the identification of epicardial enhancers activated during heart development and injury. Epicardial activation of these enhancers depends on a combinatorial transcriptional code centered on CCAAT/enhancer binding protein (C/EBP) transcription factors. Disruption of C/EBP signaling in the adult epicardium reduced injury-induced neutrophil infiltration and improved cardiac function. These findings reveal a transcriptional basis for epicardial activation and heart injury, providing a platform for enhancing cardiac regeneration.

Asunto(s)

Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Regulación de la Expresión Génica , Corazón/fisiopatología , Infarto del Miocardio/genética , Daño por Reperfusión Miocárdica/genética , Pericardio/embriología , Pericardio/metabolismo , Aldehído Oxidorreductasas/genética , Aldehído Oxidorreductasas/metabolismo , Animales , Sitios de Unión , Proteína beta Potenciadora de Unión a CCAAT/genética , Proteína beta Potenciadora de Unión a CCAAT/metabolismo , Proteína delta de Unión al Potenciador CCAAT/genética , Proteína delta de Unión al Potenciador CCAAT/metabolismo , Proteínas Potenciadoras de Unión a CCAAT/genética , Elementos de Facilitación Genéticos , Femenino , Regulación del Desarrollo de la Expresión Génica , Corazón/embriología , Masculino , Ratones , Ratones Transgénicos , Modelos Genéticos , Contracción Miocárdica , Infarto del Miocardio/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Infiltración Neutrófila , Análisis de Secuencia por Matrices de Oligonucleótidos , Técnicas de Cultivo de Órganos , Pericardio/citología , Transducción de Señal , Uroplaquina III/genética , Uroplaquina III/metabolismo , Remodelación Ventricular , Proteínas WT1/genética , Proteínas WT1/metabolismo

RESUMEN

The adult mammalian heart possesses little regenerative potential following injury. Fibrosis due to activation of cardiac fibroblasts impedes cardiac regeneration and contributes to loss of contractile function, pathological remodelling and susceptibility to arrhythmias. Cardiac fibroblasts account for a majority of cells in the heart and represent a potential cellular source for restoration of cardiac function following injury through phenotypic reprogramming to a myocardial cell fate. Here we show that four transcription factors, GATA4, HAND2, MEF2C and TBX5, can cooperatively reprogram adult mouse tail-tip and cardiac fibroblasts into beating cardiac-like myocytes in vitro. Forced expression of these factors in dividing non-cardiomyocytes in mice reprograms these cells into functional cardiac-like myocytes, improves cardiac function and reduces adverse ventricular remodelling following myocardial infarction. Our results suggest a strategy for cardiac repair through reprogramming fibroblasts resident in the heart with cardiogenic transcription factors or other molecules.

Asunto(s)

Transdiferenciación Celular , Reprogramación Celular , Fibroblastos/citología , Corazón/fisiología , Infarto del Miocardio/terapia , Miocitos Cardíacos/citología , Factores de Transcripción/metabolismo , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Linaje de la Célula , Fibroblastos/fisiología , Corazón/fisiopatología , Ratones , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Miocardio/citología , Miocardio/patología , Miocitos Cardíacos/fisiología , Fenotipo , Medicina Regenerativa/métodos , Proteína de Unión al Calcio S100A4 , Proteínas S100/genética , Proteínas S100/metabolismo , Cola (estructura animal)/citología , Factores de Transcripción/genética

RESUMEN

Iridium (III) 2-phenylpyridine (ppy) complexes with two suitable monodentate L ligands [Ir(ppy)2(L)2]⁺ (ppy = 2-phenylpyridine, py = pyridine, L = 4-pyCN 1, 4-pyCHO 2, 4-pyCl 3, py 4, 4-pyNH2 5) were studied by density functional theory (DFT) and time-dependent DFT methods. The influences of ligands L on the electronic structure and photophysical properties were investigated in detail. The compositions and energy levels of the lowest unoccupied molecular orbital (LUMO) are changed more significantly than those of the highest occupied molecular (HOMO) by tuning L ligands. With the electronegativity decrease of L ligands 4-pyCN > 4-pyCHO > 4-pyCl > py > 4-pyNH2, the LUMO distributing changes from py to ppy, and the absorptions have an obvious red shift. The calculated results showed that the transition character of the absorption and emission can be changed by adjusting the electronegativity of the L ligands. In addition, no solvent effect was observed in the absorptions and emissions.

Asunto(s)

Simulación por Computador , Electrones , Iridio/química , Luz , Modelos Moleculares , Piridinas/química , Absorción , Ligandos , Luminiscencia , Conformación Molecular , Teoría Cuántica , Solventes/química , Análisis Espectral , Termodinámica